Quantification of Biopharmaceutically Relevant Nonionic Surfactant Excipients Using Benchtop qNMR.

Nonionic surfactant excipients (NISEs) are commonly added to biologics formulations to mitigate the effects of stress incurred by the active biotherapeutic during manufacturing, transport, and storage. During manufacturing, NISEs are added by dilution of a stock solution directly into a protein formulation, and their accurate addition is critical in maintaining the quality and integrity of the drug product and thus ensuring patient safety. This is especially true for the common NISEs, polysorbates 20 and 80 (PS20 and PS80, respectively) and poloxamer 188 (P188). With the increasing diversity of biologic modalities within modern pharmaceutical pipelines, there is thus a critical need to develop and deploy convenient and user-accessible analytical techniques that can rapidly and reliably quantify these NISEs under biopharmaceutically relevant conditions. We thus pursued 60 MHz benchtop quantitative NMR (qNMR) as a nondestructive and user-friendly analytical technique for the quantification of PS20, PS80, and P188 under such conditions. We demonstrated the ability of benchtop qNMR (1) to quantify simulated PS20, PS80, and P188 stock solutions representative of those used during the drug substance (DS) formulation step in biomanufacturing and (2) to quantify these NISEs at and below their target concentrations (≤0.025% w/v) directly in biologics formulations containing histidine, sucrose, and one of three biotherapeutic modalities (monoclonal antibody, antibody-drug conjugate, and Fc-fusion protein). Our results demonstrate that benchtop qNMR offers a fit-for-purpose, reliable, user-friendly, and green analytical route by which NISE of interest to the biopharmaceutical industry may be readily and reliably quantified. We conclude that benchtop qNMR has the potential to be applied to other excipient formulation components in the presence of various biological modalities as well as the potential for routine integration within analytical and QC laboratories across pharmaceutical development and manufacturing sites.

Quantitative Investigation on Exposure to Potentially Harmful Excipients by Injection Drug Administration in Children Under 2 Years of Age and Analysis of Association with Adverse Events: A Single-Center, Retrospective Observational Study.

INTRODUCTION: Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2 years of age. MATERIALS AND METHODS: As a single-center observational study, children aged 0-23 months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs. RESULTS AND DISCUSSION: 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63 years (interquartile range [IQR] 0.1-1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary.

Quantitative analysis of drug tablet aging by fast hyper-spectral stimulated Raman scattering microscopy.

Pharmaceutical development of solid-state formulations requires testing active pharmaceutical ingredients (API) and excipients for uniformity and stability. Solid-state properties such as component distribution and grain size are crucial factors that influence the dissolution profile, which greatly affect drug efficacy and toxicity, and can only be analyzed spatially by chemical imaging (CI) techniques. Current CI techniques such as near infrared microscopy and confocal Raman spectroscopy are capable of high chemical and spatial resolution but cannot achieve the measurement speeds necessary for integration into the pharmaceutical production and quality assurance processes. To fill this gap, we demonstrate fast chemical imaging by epi-detected sparse spectral sampling stimulated Raman scattering to quantify API and excipient degradation and distribution.

Online Coupling of Size Exclusion Chromatography to Capillary Enhanced Raman Spectroscopy for the Analysis of Proteins and Biopharmaceutical Drug Products.

The online coupling of size exclusion chromatography (SEC) to capillary enhanced Raman spectroscopy (CERS) based on a liquid core waveguide (LCW) flow cell was applied for the first time to assess the higher-order structure of different proteins. This setup allows recording of Raman spectra of the monomeric protein within complex mixtures, since SEC enables the separation of the monomeric protein from matrix components such as excipients of a biopharmaceutical product and higher molecular weight species (e.g., aggregates). The acquired Raman spectra were used for structural elucidation of well characterized proteins such as bovine serum albumin, hen egg white lysozyme, and ß-lactoglobulin and of the monoclonal antibody rituximab in a medicinal product. Additionally, the CERS detection of the disaccharide sucrose, which is used as a stabilizing excipient, was quantified to achieve a limit of detection (LOD) of 120 µg and a limit of quantification (LOQ) of 363 µg injected on the column.

Sonication and heat-mediated synthesis, characterization and larvicidal activity of sericin-based silver nanoparticles against dengue vector (Aedes aegypti).

Fabrication, characterization and evaluation of the larvicidal potential of novel silk protein (sericin)-based silver nanoparticles (Se-AgNPs) were the prime motives of the designed study. Furthermore, investigation of the sericin as natural reducing or stabilizing agent was another objective behind this study. Se-AgNPs were synthesized using sonication and heat. Fabricated Se-AgNPs were characterized using particle size analyzer, UV spectrophotometry, FTIR and SEM which confirmed the fabrication of the Se-AgNPs. Size of sonication-mediated Se-AgNPs was smaller (7.49 nm) than heat-assisted Se-AgNPs (53.6 nm). Being smallest in size, sonication-assisted Se-AgNPs revealed the significantly highest (F4,10 = 39.20, p = .00) larvicidal activity against fourth instar lab and field larvae (F4,10 = 1864, p = .00) of dengue vector (Aedes aegypti) followed by heat-assisted Se-AgNPs and positive control (temephos). Non-significant larvicidal activity was showed by silver (without sericin) which made the temperature stability of silver, debatable. Furthermore, findings of biochemical assays (glutathione-S transferase, esterase, and acetylcholinesterase) showed the levels of resistance in field strain larvae. Aforementioned findings of the study suggests the sonication as the best method for synthesis of Se-AgNPs while the larvicidal activity is inversely proportional to the size of Se-AgNPs, i.e., smallest the size, highest the larvicidal activity. Conclusively, status of the sericin as a natural reducing/stabilizing agent has been endorsed by the findings of this study. RESEARCH HIGHLIGHTS: Incorporation of biocompatible and inexpensive sericin as a capping/reducing agent for synthesis of Se-AgNPs. A novel sonication method was used for the fabrication of Se-AgNPs which were thoroughly characterized by particle size analyzer, UV-visible spectrophotometry, SEM and FTIR. Analysis of enzymatic (GSTs, ESTs) levels in field and lab strains of Aedes aegypti larvae for evaluation of insecticides resistance.

Chemical modulation of microtubule structure through the laulimalide/peloruside site.

Taxanes are microtubule-stabilizing agents used in the treatment of many solid tumors, but they often involve side effects affecting the peripheral nervous system. It has been proposed that this could be related to structural modifications on the filament upon drug binding. Alternatively, laulimalide and peloruside bind to a different site also inducing stabilization, but they have not been exploited in clinics. Here, we use a combination of the parental natural compounds and derived analogs to unravel the stabilization mechanism through this site. These drugs settle lateral interactions without engaging the M loop, which is part of the key and lock involved in the inter-protofilament contacts. Importantly, these drugs can modulate the angle between protofilaments, producing microtubules of different diameters. Among the compounds studied, we have found some showing low cytotoxicity and able to induce stabilization without compromising microtubule native structure. This opens the window of new applications for microtubule-stabilizing agents beyond cancer treatment.

N-Nitrosodimethylamine formation in metformin hydrochloride sustained-release tablets: Effects of metformin and hypromellose used in drug product formulation.

In recent years, nitrosamines have been discovered in some types of drug products that becomes a current regulatory hotspot, and have attracted a lot attention from both regulatory authorities and industry. This manuscript provided an industry perspective on the nitrosamines research. A liquid chromatography coupled with tandem mass spectrometry（LC-MS/MS）method was developed and applied for the quantification of N-nitrosodimethylamine (NDMA) in metformin hydrochloride sustained-release tablets (MET). The key factors resulting in the NDMA formation in MET were identified through forced degradation and drug-excipient studies, which included high temperature, dimethylamine, strong alkali and oxidation conditions, peroxide and alkaline components contained in the formulation as well as the nitrite and nitrate impurities that might be presented in certain excipients. Further, API particle size and water content of the drug product would also affect the growth rate of NDMA. Therefore, the following mitigation strategies to reduce the risk of nitrosamines in the finished drug product are proposed in this manuscript: 1) avoid the use of excipients containing nitrite, nitrate and peroxide impurities; 2) avoid high temperature and strong alkaline environment in the production and storage condition; 3) maintain an appropriate water content level in the formulation. Based on the above principles, it was recommended to add antioxidant or incorporate excipient such as Na2CO3 to modify the formulation pH to weak basic environment in the formulation of MET, which can could effectively prevent formation of NDMA in the stability process.

Fast Compressive Raman Imaging of Polymorph Molecules and Excipients in Pharmaceutical Tablets.

We implement a near-infrared (NIR) version of compressive Raman imaging that incorporates a digital micromirror device (DMD) and a single-pixel detector for fast chemometric analysis and microscopic imaging. The NIR compressive Raman system is successfully used to detect and image active pharmaceutical ingredients exhibiting polymorphism within compact pharmaceutical tablets. We report the chemical imaging of a mixture of two clopidogrel polymorphs and three excipients in solid tablets with a pixel dwell time of 2.5 ms (0.5 ms per species). These results open the road to fast pharmaceutical tablet quality control imaging using compressive Raman technology.

A novel approach for the quantification of paclitaxel loaded in ethyl cellulose/kollicoat and ethylcellulose/eudragit colloidal particles by UPLC-PDA.

An optimized rapid reversed phase ultra-performance liquid chromatography (UPLC-PDA) method has been developed and validated for precise and accurate quantification of paclitaxel in drug delivery systems. The chromatographic separation was attained on L1 (USP) column (2.1 ×50 mm, 1.7µm) with an isocratic mobile phase comprised of acetonitrile and water (1:1; flow rate 0.6 mL/min) and detection was executed at 227 nm by PDA detector. The proposed UPLC-PDA method is found to be rapid with retention time of 1.37 min, selective with homogenous peaks and sensitive with Limit of Detection (LOD) of 0.08µg/mL and Limit of Quantification (LOQ) of 2.6µg/mL. The method showed excellent linearity (R2>0.998) over the range of 0.1 to 0.4mg/mL and applied for the paclitaxel quantification in different formulations with no inference of excipients. Thus, the proposed approach has potential for rapid estimation of drug purity, assay and release profile from pharmaceutical preparations.

Study on Hydration and Dehydration of Ezetimibe by Terahertz Spectroscopy with Humidity-Controlled Measurements and Theoretical Analysis.

Understanding the solid-state transitions of active pharmaceutical ingredients (APIs) is essential for quality control since differences in their forms affect the bioavailability of APIs. Terahertz (THz) frequency-domain spectroscopy is suitable for such an application since it can sensitively probe the lattice phonon modes originating in the crystal structures. THz absorption spectra were obtained for ezetimibe (EZT) and ezetimibe monohydrate (EZT-MH), which have similar crystalline structures and belong to the same space group. The observed absorption spectrum of EZT matched well with the solid-state density functional theory (ss-DFT)-simulated spectrum for the structures at 0 K and room temperature (modeled using constrained unit cell volumes). However for EZT-MH, the ss-DFT spectrum of the room-temperature structure showed better correlation with the experimental THz spectrum than that of the simulated spectrum of the 0 K structures, suggesting that the EZT-MH crystal has greater anharmonic character. Gibbs free-energy curves were calculated, and EZT-MH was found to be more stable than pure EZT and water in a broad temperature range. The hydrate stability may be influenced by the existence of more hydrogen bonds in EZT-MH. The hydration and dehydration of EZT in a pure API tablet and formulation tablets were monitored using a THz spectrometer with a humidity-controlled sample chamber. The effect of the excipient in the formulation tablet on hydration was successfully confirmed by showing that the solid-state transition of the API with excipients is significantly slower than that without it. Under a relative humidity of 60%, hydration of EZT in a pure EZT tablet occurred in 200 min, while the hydration of EZT in a formulation tablet was 50 times slower.

Application of Confocal Raman Microscopy for the Characterization of Topical Semisolid Formulations and their Penetration into Human Skin Ex Vivo.

PURPOSE: The quality testing and approval procedure for most pharmaceutical products is a streamlined process with standardized procedures for the determination of critical quality attributes. However, the evaluation of semisolid dosage forms for topical drug delivery remains a challenging task. The work presented here highlights confocal Raman microscopy (CRM) as a valuable tool for the characterization of such products. METHODS: CRM, a laser-based method, combining chemically-selective analysis and high resolution imaging, is used for the evaluation of different commercially available topical acyclovir creams. RESULTS: We show that CRM enables the spatially resolved analysis of microstructural features of semisolid products and provides insights into drug distribution and polymorphic state as well as the composition and arrangement of excipients. Further, we explore how CRM can be used to monitor phase separation and to study skin penetration and the interaction with fresh and cryopreserved excised human skin tissue. CONCLUSION: This study presents a comprehensive overview and illustration of how CRM can facilitate several types of key analyses of semisolid topical formulations and of their interaction with their biological target site, illustrating that CRM is a useful tool for research, development as well as for quality testing in the pharmaceutical industry.

Pharmaceutical evaluation of compounded furosemide capsules and excipient performance

Abstract Compounding pharmacies play an important role not only in compounding personalized formulations, but also preparing drugs at the same concentration and dosage as those from commercial manufacturers. The excipients used in compounding are generally standardized for many drugs, however they do not consider the intrinsic properties, such as the poor water solubility, of each substance. The excipient performance of commercially available compounded furosemide capsules in 7 compounding pharmacies from Manaus was evaluated and compared them to the performance of the reference medicinal product (Lasix® tablets) and 2 batches of capsules made in-house (T2 and T4) with a standardized excipient. All batches were subjected to tests for weight variation, assay, uniformity of dosage units, disintegration and dissolution profile. Of the 7 different compound formulas acquired in the compounding pharmacies, only 2 passed all tests. Most formulas passed the tests for weight determination, disintegration time and assay, however batches from 2 establishments failed in regards to the uniformity of the content and 5 batches failed the dissolution test. The reference medicinal product was approved in all tests, as were the T2 capsules made in-house with drug-excipient ratio 1:2. These results confirm the importance of the excipient composition, especially for poorly soluble drugs.

Scaling Down Large-Scale Thawing of Monoclonal Antibody Solutions: 3D Temperature Profiles, Changes in Concentration, and Density Gradients.

PURPOSE: Scale-down devices (SDD) are designed to simulate large-scale thawing of protein drug substance, but require only a fraction of the material. To evaluate the performance of a new SDD that aims to predict thawing in large-scale 2 L bottles, we characterised 3D temperature profiles and changes in concentration and density in comparison to 125 mL and 2 L bottles. Differences in diffusion between a monoclonal antibody (mAb) and histidine buffer after thawing were examined. METHODS: Temperature profiles at six distinct positions were recorded with type T thermocouples. Size-exclusion chromatography allowed quantification of mAb and histidine. Polysorbate 80 was quantified using a fluorescent dye assay. In addition, the solution's density at different locations in bottles and the SDD was identified. RESULTS: The temperature profiles in the SDD and the large-scale 2 L bottle during thawing were similar. Significant concentration gradients were detected in the 2 L bottle leading to marked density gradients. The SDD slightly overestimated the dilution in the top region and the maximum concentrations at the bottom. Fast diffusion resulted in rapid equilibration of histidine. CONCLUSION: The innovative SDD allows a realistic characterisation and helps to understand thawing processes of mAb solutions in large-scale 2 L bottles. Only a fraction of material is needed to gain insights into the thawing behaviour that is associated with several possible detrimental limitations.

Alternatives to titanium dioxide in tablet coating.

Titanium dioxide (TiO2) is one of the most commonly used pharmaceutical excipients. It is widely used as a white pigment in tablet and pellet coatings. However, it has recently been under massive criticism as a number of studies suggest a cancerogenic potential. It can therefore no longer be taken for granted that TiO2 will continue to be universally available for drug products. Finding suitable alternatives is hence of special relevance. In this study, a number of different pigments were coated on tablets and their covering potential analyzed. None of the alternative pigments showed comparable effectiveness and efficiency to TiO2, though the CaCO3/CaHPO4-based coating showed the second-best results. Regarding the ability to protect photosensitive active ingredients, ZnO showed a comparable potential as TiO2, while all other pigments failed. Using the alternative pigments as markers for in-line Raman spectroscopy as a process analytical technology was challenging and led to increased prediction errors. Again, the CaCO3/CaHPO4-based coating was the only of the tested alternatives with satisfying results, while all other pigments led to unacceptably high prediction errors.

[Effect of Shelf Life on the Physical Stability of Suspended Ophthalmic Solutions].

Quality changes associated with physical changes in suspended eye drops are difficult to predict. In this study, we attempted to evaluate the aggregation and redispersability in commercially available suspended eye drops (fluorometholone ophthalmic solutions). The 0.1% fluorometholone ophthalmic solutions (the original product and 4 generic products) were gently mixed by hand after short-term (4 months) or long-term (40 months) storage, and the drug concentration in the first drop and physical stability (redispersability and particle size) were measured. All eye drops produced a cloudy precipitate on the bottom surface of the container, and the amount of precipitate decreased with mixing time. The drug concentration per drop in the original product was approximately 70% of the labeled value after mixing 10 times, and the drug particle size was approximately 4 µm. After mixing the generic products stored short-term 10 times, the concentration ranged from less than 50% to almost 100%. In addition, some generic products after long-term storage had a reduced redispersion ability and labeled concentration. These results suggested that at least 10 mixing were required before the using of fluorometholone original product. In addition, some generic products may not provide sufficient drug exposure even when mixed in the same manner as the original products.

Preparation and evaluation of vancomycin spray-dried powders for pulmonary delivery.

The aim of the current study was to achieve a dry powder formulation of vancomycin by spray drying whilst evaluating the effect of pH and excipient type and percentage used in formulation on particle characteristics and aerosolization performance. A D-optimal design was applied to optimize the formulation comprising vancomycin and two main excipient groups; a carbohydrate bulking agent (lactose, mannitol or trehalose) and a second excipient (hydroxypropyl beta-cyclodextrin or L-leucine) at pH 4 and 7. The physicochemical properties of particles (size, morphology, crystallinity state, residual moisture content), stability, and aerosolization characteristics were investigated. Using the combination of two excipients increased the fine particle fraction of powder emitted from an Aerolizer® device at a flow rate of 60 L/min. Hydroxypropyl beta-cyclodextrin showed more potential than L-leucine in aerosolization capabilities. Stability studies over 3 months of storage in 40 °C and 75% relative humidity suggested a good physical stability of the optimized formulation containing 17.39% hydroxypropyl beta-cyclodextrin along with 29.61% trehalose relative to the amount of drug at pH 4. Use of two excipients including trehalose and hydroxypropyl beta-cyclodextrin with a total weight ratio of 47% relative to the amount of drug is appropriate for the preparation of vancomycin dry powder formulation for inhalation.

Investigating the root cause of N-nitrosodimethylamine formation in metformin pharmaceutical products.

BACKGROUND: FDA limited N-nitrosodimethylamine (NDMA) - a carcinogenic impurity formed during metformin (MET) tablets manufacturing - level to 96 ng/day; a step which led to recall of MET products. This work aims to investigate the root cause of NDMA formation during MET tablets manufacturing. RESEARCH DESIGN AND METHODS: We focused on three main contributing causes: use of water and heat during intra-granulation, and the nitrite/nitrate quantities in excipients. Thirteen MET tablet formulations (immediate or sustained-release) were manufactured, on batch level. Each batch was manufactured using one excipient and excluding one cause at a time and NDMA level was assayed. RESULTS: NDMA traces were undetectable in MET tablets manufactured using polyvinyl pyrrolidone or hydroxypropyl cellulose SSL, even when water and/or heat were employed during intra-granulation. Levels of NDMA in MET tablets with hydroxypropyl methyl cellulose (HPMC) E5 or carboxymethyl cellulose sodium 4000 were 67.08 ± 2.3 and 66.21 ± 2.5 ng/day, in the presence of water and/or heat. No impact of employing extra-granular PolyoxTM, HPMC E5 or HPMC K15 on NDMA formation, despite the high nitrite and nitrate content in these excipients. CONCLUSIONS: Water, heat, and excipients' nitrite and nitrate levels are the key players, which should collectively exist, to cause NDMA formation during MET tablets manufacturing.

Introduction and clearance of beta-glucan in the downstream processing of monoclonal antibodies.

ß-Glucan process-related impurities can be introduced into biopharmaceutical products via upstream or downstream processing or via excipients. This study obtained a comprehensive process-mapping dataset for five monoclonal antibodies to assess ß-glucan introduction and clearance during development and production runs at various scales. Overall, 198 data points were available for analysis. The greatest ß-glucan concentrations were found in the depth-filtration filtrate (37-2,745 pg/ml). Load volume correlated with ß-glucan concentration in the filtrate, whereas flush volume was of secondary importance. Cation-exchange chromatography significantly cleared ß-glucans. Furthermore, ß-glucan leaching from the Planova 20N virus removal filter was reduced by increasing the flush volume (1 vs. 10 L/m2 ). ß-glucan concentrations after filter flush with 10 L/m2 were consistently <10 pg/ml. No or only limited ß-glucan clearance was attained via ultrafiltration/diafiltration (UF/DF). However, during the first run with monoclonal antibody (mAb) 4, ß-glucan concentration in the UF/DF retentate was 10.8 pg/mg, potentially due to ß-glucan leaching from the first run with a regenerated cellulose membrane. Overall, ß-glucan levels in the final mAb drug substance were 1-12 pg/mg. Assuming high doses of 1,000-5,000 mg, a ß-glucan contamination at 20 pg/mg would translate to 20-100 ng/dose, which is below the previously suggested threshold for product safety (≤500 ng/dose).

An improved method for the simultaneous determination of water uptake and swelling of tablets.

Water uptake and swelling of tablets are processes occurring during active pharmaceutical ingredient (API) release. Thereby, disintegration is promoted and the enhanced exposure of API surface area to the release medium facilitates API dissolution. An experimental set-up for the simultaneous and time-resolved determination of water uptake and swelling of tablets has been developed. Water uptake was determined with a balance and swelling was determined with a camera. To validate the gravimetrical analysis, real-time water uptake measurements with inert test specimens were performed. The standard deviation of these measurements was considered to depict precision. A complementary gravimetrical analysis was employed to determine accuracy. For both, precision and accuracy, a maximum deviation of 6% was found. An algorithm for the symmetry-based 3D volume reconstruction was applied to obtain volumes of the tablets from 2D images. X-ray micro computed tomography was used to validate the accuracy and the determined volumes were in good accordance within 6% deviation. A case study with binary formulations of a filler and disintegrants confirmed reproducibility and demonstrated the ability of the method to discriminate formulation characteristics, such as disintegrant type, composition and porosity for water uptake and swelling with the necessary temporal resolution.

Comparative Physicochemical Evaluation of Starch Extracted from Pearl millet seeds grown in Sudan as a Pharmaceutical Excipient against Maize and Potato Starch, using Paracetamol as a model drug.

OBJECTIVES: The aim of the current study was to compare the physicochemical and disintegrant properties of pearl millet starch with other starches using paracetamol as model drug. METHODOLOGY: Determination of percentage yield, Physicochemical, micrometrics characteristics of starch/granules, drug excipients compatibility studies and evaluation of prepared paracetamol tablets were measured using official techniques. RESULTS: The yield of the millet starch ranged from 30 to 40%. Moisture content 8.77%, pH 5.7, Swelling capacity 1.2, Hydration capacity 1.748, Moisture uptake 11.8%, Amylose 24.6%, with poor flowability and compressibility. No significant difference in hardness, friability% & disintegration times for formulations containing millet starch to that containing potato and maize starch (P>0.05). CONCLUSION: From the study, Millet seeds locally cultivated in Sudan gave a high yield of starch, has same physicochemical properties as maize and potato starch so can be used as an alternative to those starches.